This project consists of continuing studies of the chemistry, structure, epidemiology, immunology and pathology of human and related hepatitis viruses. The foal of such studies is the control of human viral hepatitis by application of the most appropriate methods, including active and passive immunization, chemotherapy and interdiction of spread of the virus. Progress: Hepatitis A virus has been isolated directly from the stool of a patient into primary African green monkey kidney cell culture, a substrate suitable for vaccine development. The RNA genome of hepatitis A virus is being cloned in E. coli. Modifications in hepatitis B subunit vaccine have resulted in a highly immunogenic and safe preparation that produces a seroconversion in approximately 60% of vaccinees within two weeks of vaccination and in 95% following completion of the vaccination schedule. A "new" antigen, possibly reflecting the presence of a "transforming" gene, has been found in certain cells that contain integrated HBV genome. Non-A, non-B hepatitis agents have been transmitted to chimpanzees and, probably marmosets, and ultrastructural changes that appear to be specific for non-A, non-B hepatitis have been identified. Evidence has been obtained for the existence of an epidemic form of non-A, non-B hepatitis in India. Attempts to transmit the virus to chimpanzees are currently in progress.